Project Summary: Despite making up approximately 90 percent of the cells in the human body, the contributions of human-associated microbes to overall human health remain largely unknown. Researchers are now beginning to study the complex interactions between these microbes and their human hosts. Technological advances coupled with an increased interest in this new frontier in health-related research, including the creation of the Human Microbiome Project, has already yielded interesting insight into diverse biological processes. In this application, I will describe a plan to probe the human microbiome for genetic elements that have implication for human health. As a proof of principle, I will describe a set of experiments to identify antibiotic resistance elements present in a community of soil bacteria. I will then use this data to identify homologous resistance elements within the human microbiome. In addition to enriching our knowledge of the genetic determinants of antibiotic resistance, this work will serve as a model for the application of metagenomic technology to the assessment of human health. Public Health Relevance: The bacteria that live in the human gut and mouth are major determinants in the health of a person. Studying the biochemical properties of these bacteria will give insight into human disease. In this work, I plan to use a new approach to identify genes within the human-associated bacterial community that confer antibiotic resistance. The methodology outlined in this application will serve as a guide for the diagnosis and treatment of other diseases linked to the bacteria present within people.